As a result of widespread use of illegal drugs in our society, employers and government agencies have initiated regular drug testing programs which subject potential employees to urine analysis prior to their employment. Such drug testing has become commonplace in the work force, such as the Federal National Institute of Drug Testing (NIDA) program. Often an employer's decision to hire a particular applicant is dependent on the individual passing such a test.
These drug tests are most commonly performed at a laboratory or lab collection site. The most common urine drug tests used today by employers check for the presence of illegal drugs or their metabolites, at certain concentration levels. Drug metabolites are the chemical derivatives of a drug after the drug has been metabolized by the body. For instance, it is not uncommon for employers to test for the presence of the marijuana THC metabolite and the cocaine metabolite in addition to marijuana and cocaine, by using either blood or urine analysis. It should be recognized that urinalysis is clearly preferred by employers and laboratories due to its lower costs, lack of invasiveness for the test subjects, and reduced health risks. If a tested individual has less than a predefined concentration (or cutoff level) of the illegal substance in their urine sample, the drug test result is "negative", and the individual passes the test. If the concentration of the substance in the sample is higher than the cutoff value, the result is "positive" and the individual fails the test.
While such drug testing has curbed some use of illegal substances in the work place, many individuals continue to use these drugs despite the possible physiological and social consequences. These individuals often attempt to adulterate their urine specimens during the test procedure, adulteration being the altering by a patient of his or her urine in an effort to prevent detection of an illicit drug in the urine specimen. This type of activity takes many forms and is often successful in affecting the outcome of drug tests, thereby creating a "false negative" result.
The scientific literature has documented at least two different types of adulteration activities. The first type of activity occurs at the drug testing site and is directed to altering the test result by changing the actual urine sample in some fashion. This activity includes adding a foreign substance directly to the urine sample while it is in a specimen container, such as water, bleach, vinegar or a chemical agent; or substituting a foreign urine specimen for that of the person being tested. The addition of these substances can have a direct effect on the drug test chemical analysis and hence the result. It has been demonstrated that while such activity may be effective in altering the outcome of a drug test, such activity can either be discovered or discouraged through close supervision at the test site or by visual inspection of the urine specimen itself. Often the addition of foreign substances to a specimen alters the appearance and characteristics of the urine. If an individual attempts to substitute a foreign specimen for his/her own, a temperature analysis often tips the test taker off to the scheme. If an individual adds a foreign substance to the specimen, a change in color, clarity, odor, temperature, or pH will indicate the addition of the foreign substance.
The second type of adulteration activity involves the indirect addition of a foreign substance into the urine via ingestion prior to giving the urine sample. The substance ingested is eliminated in the urine sample along with the normal body waste and can have a direct effect on the drug test chemical analysis. This type of adulteration is often more difficult to detect and address because the urine appears normal. The temperature and color of the specimen are within an acceptable range. Examples of this type of activity include drinking large quantities of water prior to taking a urine test or ingesting a naturally derived or manmade chemical compound that affects testing analysis.
By drinking large quantities of water prior to testing, an individual effectively dilutes the concentration of any drug appearing in their urine, potentially lowering the drug concentration below the detectable cutoff level. In this regard, it is important to note that the relative concentration of metabolites in urine is a function of detection time. By hydrating oneself prior to taking a drug test, the amount of drug metabolites in urine is necessarily decreased. However, the amounts of substances in the urine normally produced through the elimination of waste are found even in the hydrated sample, at the same ratio that they would be expected to be found if the kidneys were functioning normally. This is significant since drug tests have a specific cut-off value which indicate a positive or negative result. The effect of drinking large quantities of water (or diuresis) can cause dilution of a urine sample up to ten-fold, which, depending on the concentration of the drug could lead to a false negative result. However, the other substances in urine will still be found in their normal percentages for the amount of water passing through the kidneys.
Essentially, in diuresis, the concentration of drug metabolites for the amount of volume of urine produced can fall below the cut-off value, which can create a false negative result. For example, the drug cutoff level for a particular drug metabolite may be 100 mg/ml. If the urine is diluted down 2-4 times (and the individual had the cut-off level of metabolites in their system before dilution), the individual will appear to pass the test, even though the individual in fact has enough drug in their system to normally fail a drug test. This false negative could then lead to the inappropriate step of hiring the individual. It should be noted however, that sometimes an individual who has drank large quantities of water prior to testing produces a urine which is so dilute that it resembles water in appearance. In this scenario, a drug testing center can reconstruct the particular circumstances by which the individual diluted the sample.
Alternatively, individuals may take diuretics such as water pills to dilute their urine specimen. While the drinking of excessive fluid often results in increased urine from an individual, the water which passes through the individual's kidneys is filtered at the normal rate. In contrast, a diuretic forces greater amounts of fluid from individual cells in the body through the kidneys, resulting in an increased amount of water in the urine sample without a corresponding amount of secondary elements present. In this situation, the ratio of fluid to the amount of secondary substances normally present in the urine would be artificially high. The diuretic effectively dilutes the concentration of illegal substances, but without the need to drink excessive amounts of fluid. While diuretics do not interfere with the chemical mechanics of the drug test, they do have the capability of diluting the concentration of the drug to a level which is either not detectable or is below the established administrative cut-off levels. Some diuretics are very potent and fast acting, lasting for many hours. These can be used to cause significant dilution of the drug in the urine in a very short time period.
As a result of these types of activities, laboratory tests have been developed to determine if urine has been adulterated by dilution. Several properties of the urine are measured in these tests to evaluate whether the urine is adulterated in this manner. Such include testing the amount of ions in the urine (ionic strength), since urine typically includes large amounts of ions, or testing the conductivity of urine, since urine is typically comprised of large amounts of electrically charged particles (ions). Additional tests include pH testing, since urine normally has a narrow pH range, testing the creatinine concentration of the urine, since the body normally eliminates a predictable amount of creatinine, and specific gravity testing, since the body normally eliminates a predictable quantity of solids through the urine.
For example, when checking urine pH, pH is measured as with the use of a pH data/logger-type meter available from Oakton, to see if the urine specimen has a pH within the normally expected pH range of 4.5 to 8.5. Alternatively, pH may be measured through chemical analysis. Chemical pH test methods, exemplified by the pHPERFECT.TM. test of Chimera Research & Chemical, Inc., is based on the indicator principle which gives a broad range of color intensity covering the entire urinary pH range.
Urine specific gravity (SG) may be measured by methods such as refractometry or by ionic strength in order to determine if it is in the normal range. Ionic strength/specific gravity tests may also be through chemical methods such as sGPERFECT.TM., also from Chimera, but based on the pKa change of pretreated polyelectrolytes in response to ionic concentration of the test sample. The reaction produces a color change with increasing concentration of the sample.
Creatinine levels may be measured by a creatinine analyzer such as the TDx REA Creatinine System available from Abbott Laboratories to determine if it is in the normal range or through a chemical test such as CR PERFECT.TM., also from Chimera. Of the various measures however, urinary creatinine level is generally the most useful indicator as to whether a spot sample is that of the patient or of someone else, providing comparative historical data has already been developed for the particular individual.
Once pH, specific gravity, and creatinine level values for the spot urine sample are obtained for a particular individual, comparisons can be made between the sample in question and values previously measured if already available, or in the alternative, comparisons may be made between the sample and a range of established values for a normal testing population. If the test results fall within the acceptable range, the sample is determined to be unadulterated.
It should be noted that the chemical tests commercially available from companies such as Chimera are intended for use as screening tools for determining abnormally high or low urine SG values (based on the presence of ions in the urine) outside the ranges of 1.003 and 1.030 for use with the Olympus, Hitachi, Monarch and other automated systems. Such drug tests are particularly effective in detecting abnormally high specific gravity values if those values are based on increased ions in the urine resulting from certain diuretic use (such as from water pills). Specific chemical testing kits such as the sGPERFECT have different test ranges to determine specific ranges of SG values. Such tests have limited practical value as they are range specific, and often fail to tag adulterated urine specimens with normal specific gravity values.
Furthermore, while the current test methods of urine adulteration are somewhat effective, there are times when the standard ionic strength, pH, and creatinine tests fail to detect urine adulteration by exogenous or endogenous diuretics. Exogenous diuretics are substances which are added to the body either through ingestion or a medical procedure which add solids to the urine that are not detected by ionically-dependent chemical-based specific gravity tests. Urine specific gravity appears normal under these tests. Examples of such substances include iodine from contrast, radiopaque dyes from diagnostic medical procedures, and the osmotic diuretic isosorbide which deposits non-ionic solids in the urine. Endogenous diuretics are substances which function as diuretics but are naturally excreted from the body as a result of an abnormal medical condition. Endogenous diuretics add solids to the urine that are also not detected by ionically-dependent specific gravity tests. Such substances include glucose as a result of diabetes mellitus, and protein molecules from the nephrotic syndrome. Therefore, a urine sample which exhibits elevated specific gravity values on a non-ionic SG test may also not necessarily be indicative of intentional adulteration.
If a non-ionic substance (adulterant) is intentionally added to the urine indirectly through digestion/absorption, such as an osmotic diuretic, it would appear to be invisible on an ionic strength (SG) test. The SG appears normal but in actuality is higher if measured through refractometry, which detects all urinary solids. In this instance, there would be more water in the urine than normal, but the osmotic diuretic would not be found. The urine would therefore be presumed to be unadulterated, since the SG appears normal. Furthermore, the concentration of the illegal substance could be less than the cut-off value as a result of the increased water concentration caused by the diuretic, thereby creating a false negative.
While providing useful information in some instances of the presence of unusual levels of water, ions, creatinine, or solids in a specimen, current adulteration test methods have distinct drawbacks which limit there usefulness in drug testing programs. Current test methods often fail to reveal the intentional use of a diuretic to defeat a drug test. Furthermore, such test methods fail to distinguish artificially inflated specific gravity values resulting from medical conditions as opposed to osmotic diuretics. Thus, it is seen that a need remains for better methods of determining whether a urine sample has been adulterated by the use of either water pill-type diuretics or osmotic diuretics. Accordingly, it is to the provision of such improved methods that the present invention is primarily directed.